The present invention provides a substantially medication agnostic method, system and device for enhancing the safety of delivering medications and/or fluids to subjects in need thereof. There are several related aspects of the invention by means of which this comprehensive and substantially medication agnostic safety system operates, but in general, the invention provides means for monitoring the combined effects of clinical interventions and a patient's underlying clinical condition and, based on such monitoring, provides a processed output to advise medical personnel of the need for modifying the intervention(s), or, in particular scenarios, automatically initiates alternate interventions to secure the safety of the subject. For example, and without limitation, for conscious sedation and administration of opioid and other drugs, including drugs which alone or in combination with other drugs, and/or the patient's clinical condition(s) cause or can cause respiratory depression, the present system, method and apparatus: (a) monitors subject breath rate, breathing effort, as well as, optionally, a plethora of other physiologic parameters, and (b) on detection of an adverse parameter based on algorithms and limits built into the system, advises medical personnel of the need for intervention and/or automatically intervenes to, for example, shut off or diminish delivery of the opioid or other medication, and initiates non-invasive positive pressure and/or ventilation to ensure that the patient is adequately oxygenated and ventilated. When used in a clinical setting, such as in an Intensive Care Unit (ICU), where the patient is already or could be intubated, ventilation could be modified accordingly, while still deriving the benefit of the additional information available from implementation of the present system.
To date, no commercially available closed-loop system or “advisory” system exists, at least in the United States, for administration of anesthetics (see Sahinovic et al., Current Opinion in Anesthesiology, 2010, 23:734-740; see also the American Society of Anesthesiologist's comments to the FDA respecting an Application for Premarket Approval for SEDASYS™ System by Ethicon Endo-Surgery, Inc. Docket No FDA-2009-N-0664; Meeting ID 2009-4438 before FDA's Anesthesiology and Respiratory Therapy Devices Panel of the Medical Devices Advisory Committee, publicly available at http://www.asahq.org/For-Members/Practice-Management/ASA-Practice-Management-Resources/ASA-Regulatory-Comment-Letters/ASA-Comments-to-the-FDA-regarding-SEDASYS.aspx). In one aspect of the present invention, a system, method and apparatus is provided which addresses the concerns expressed by the ASA before the FDA.
In a number of scenarios, it is possible to safely infuse subjects with pharmaceutically active agents or fluids. In other scenarios, for example where a subject is to be infused with an opioid, there remains substantial danger to the subject, unless they are closely monitored, and, even then, in the absence of the safety features provided by the present device, system and method, substantial risk remains. The present invention, therefore, provides a solution to this problem, which represents a long-term critical unmet medical need.
Conventional monitoring for respiratory depression in the hospital setting involves monitoring, for example, end tidal carbon-dioxide (ETCO2). However, ETCO2 monitoring is impractical in many scenarios. For example, it is difficult to measure in ambulatory patients (non-intubated patients). It is also costly, and the relevant equipment is cumbersome. The ability to directly monitor the pharmacodynamic (PD) effects of all of the factors that may contribute to hypopnea and/or apnea is far more valuable, for example, than knowing a single physiologic measurement, such as the ETCO2. Knowing the combined effects of CO2, hypoxemia, opioids, other drugs, and physiologic state of a patient would provide much more valuable information for the patient's safety. Trending of various parameters would also be highly valuable, not only for closed-loop systems, but also for improved monitoring of patients in a hospital setting.
The present inventors have identified a number of technologies which may be adapted, as disclosed herein below in the detailed disclosure of the invention, for the particular purposes to be achieved by practice of the present invention. Thus, references to such technologies herein, and the documents in which those technologies are described, are to be considered as having been fully set forth herein.
For example, in U.S. Pat. No. 7,785,262B2, METHOD AND APPARATUS FOR DIAGNOSING RESPIRATORY DISORDERS AND DETERMINING THE DEGREE OF EXACERBATIONS, hereafter “the '262 patent”, involves the identification of peaks and troughs in plethysmograph signals, preferably acquired from a central site location of a subject, such as the nasal ala(e), identifying midpoints or minima between peaks and troughs, and using an interpolated line to represent venous impedance, permits extracting of venous impedance and capacitance to thereby obtain an low frequency (or venous impedance) component signal indicative of respiratory rate and effort, inspiratory and/or expiratory times, thereby facilitating detection of an airway obstruction or cessation of breathing event (such as obstructive sleep or central apnea). Because the details of how that method is practiced is relevant here, we note that the '262 patent discloses and claims a method of monitoring respiration in a patient by securing a probe to a central source/sensing site of a patient to generate a plethysmography signal stream, and processing the signal stream received from the probe to obtain a venous impedance component signal. As disclosed in the '262 patent, the processing of the signal stream involves identifying peaks and troughs in the signal stream, identifying midpoints or minimum values between the peaks and troughs, and generating an interpolated line connecting the midpoints or minimum values which represents the venous impedance component. The thus identified venous impedance component is extracted from the signal stream to thereby obtain a separate arterial component signal and separate venous impedance component signal. This extraction and analysis algorithm makes it possible to observe changes in the venous impedance component signal which correlate with respiratory rate, inspiratory or expiratory events, or combinations of these events in a patient. The central source site is identified as preferably being selected from the group consisting of a nasal septum, a nasal alar, a pre- or post-auricular region, a cheek, or an ear canal of the patient. Applying the '262 technology in the present invention in the context of control of medication delivery provides a powerful method for monitoring a patient's respiratory rate, respiratory effort and associated parameters, to implement appropriate interventions as necessary, and as described in detail herein below. As disclosed further herein below, such a system may be integrated into the present system, method, and device for enhanced safety in providing certain types of treatment or therapy in particular contexts. In particular, for example, in providing opioid therapy via a closed loop or “advisory” system, integration of such technology into an infusion device, optionally including in a given embodiment, any one or a combination of (a) a means for providing positive pressure ventilation, whether, preferably, via a novel non-invasive patient ventilation apparatus as described in further detail herein below, or via a more invasive intubation ventilation interface such as those known in the art, (b) a means for occluding the delivery of the medication, (c) an accelerometer, or (d) other features disclosed herein; provides enhanced safety controls.
Likewise, with respect to published US patent application US2010/0192952, herein incorporated by reference, the present invention disclosure provides significant new applications and enhancements to the devices and methods disclosed therein. US2010/0192952 discloses certain pulse oximeter/plethysmography probes designed for securement to the nose, in a stand-alone form or incorporated into a mask of an air pilot or fire-fighter, pulse oximeter/plethysmography probes designed for securement to the pre-auricular portion of a subject's ear, to the ear canal of a subject's ear, to the post-auricular portion of the subject's ear, or to the cheek of a subject's face. All of these designs are incorporated by reference into this disclosure, with the key modifications of these probes as described herein below, and the key modifications to the methods and systems disclosed herein which facilitate the safe, effective and efficient open- or closed-loop delivery of appropriate medications to the subject, dependent on the analysis of PD and/or PK signals obtained from the subject, optionally including in a given embodiment, any one or a combination of (a) a means for providing positive pressure ventilation, (b) a means for occluding the delivery of the medication, (c) an accelerometer; (d) Self Monitoring and Reporting Technology, SMART, which provides an independent means for confirming dosage, time and identity of medication administered; (e) other features disclosed herein; provides enhanced safety controls.
The modifications and enhancement disclosed herein are likewise applicable to the context's disclosed in the U.S. Pat. Nos. 6,909,912, 7,024,235, and 7,127,278, i.e. to prevent Gravity-induced Loss of Consciousness (GLOC) or Almost Loss of Consciousness (ALOC), as well as, for example, in the context of the fire-fighter. The key enhancements disclosed herein for this purpose include either an integrated or separately housed infusion system as well as enhancements achieved by coupling PPG signal acquisition and processing to nasal pressure signal acquisition and processing. In the contexts of GLOC and ALOC, for example, the present invention provides the option not only of altering the G-force induced loss or almost loss of consciousness, by setting off an alarm or interfacing with an aircraft's onboard computer, but to also, or instead, provide the option of pharmacologic intervention, e.g. by detection of GLOC or ALOC and infusing the subject with an appropriate dose, for example, of glucose, epinephrine, institution of oxygen or increased flow of oxygen or the like, or combinations thereof, calculated to avert the potentially catastrophic sequelae of a loss of consciousness in these circumstances, optionally including in a given embodiment, any one or a combination of (a) a means for providing positive pressure ventilation, (b) a means for occluding the delivery of the medication, (c) an accelerometer, (d) SMART; (e) other features disclosed herein; provides enhanced safety controls.
Similarly, the technology described in Diab U.S. Pat. No. 6,157,850 (hereafter the '850 patent) provides, in particular with respect to blood oximetry measurements, methods, systems, algorithms and apparatuses to extract meaningful physiological information. Such a system may be integrated into the present method, device, system, to enhance safety by providing relevant pharmacodynamic (PD), pharmacokinetic (PK), or both PD and PK guided infusion in particular therapeutic contexts, optionally including in a given embodiment, any one or a combination of (a) a means for providing positive pressure ventilation, (b) a means for occluding the delivery of the medication, (c) an accelerometer, or (d) other features disclosed herein; provides enhanced safety controls.
U.S. Pat. No. 7,569,030 and related Medtronic MiniMed patents (see, e.g. U.S. Pat. No. 6,827,702, and U.S. Pat. No. 6,740,972) describes a system for delivery of insulin for control of physiological glucose concentration. In these patents, however, there is very little disclosure about the “sensing device for sensing a biological state” element even for a closed loop system for delivery of insulin. The only sensing device identified is one for measuring glucose concentration. The main thrust of these patents is a system for setting safety limits for the amount of insulin provided by an infusion pump, and the ability for the user to over-ride certain limits to simulate, for example, the body's “leading insulin secretion reflex”. Other over-rides, to address medications or activity states (sleep, stress, etc), forms a central part of the disclosure. Methods for calculating delivery rates of an infusion formulation of insulin in response to a sensed glucose concentration are disclosed.
The need for dynamic modelling to control opioid administration has been recognized. See, for example, Mitsis et al., J Appl Physiol. 2009 April; 106(4):1038-49, “The effect of remifentanil on respiratory variability, evaluated with dynamic modelling”, (hereafter, “Mitsis et al.) which noted that opioid drugs disrupt signalling in the brain stem respiratory network affecting respiratory rhythm. Mitsis et al., evaluated the influence of a steady-state infusion of a model opioid, remifentanil, on respiratory variability during spontaneous respiration using dynamic linear and nonlinear models to examine the effects of remifentanil on both directions of the ventilatory loop, i.e., on the influence of natural variations in end-tidal carbon dioxide PETCO2 on ventilatory variability, (which was assessed by tidal volume (VT) and breath-to-breath ventilation i.e., the ratio of tidal volume over total breath time VT/Ttot), and vice versa. Breath-by-breath recordings of expired CO2 and respiration were made during a target-controlled infusion of remifentanil for 15 min at estimated effect site (i.e., brain tissue) concentrations of 0, 0.7, 1.1, and 1.5 ng/ml, respectively. They found that Remifentanil caused a profound increase in the duration of expiration. The obtained models revealed a decrease in the strength of the dynamic effect of PETCO2 variability on VT (the “controller” part of the ventilatory loop) and a more pronounced increase in the effect of VT variability on PETCO2 (the “plant” part of the loop). Nonlinear models explained these dynamic interrelationships better than linear models. The described approach allows detailed investigation of drug effects in the resting state at the systems level using non-invasive and minimally perturbing experimental protocols, which can closely represent real-life clinical situations.
By contrast, the present invention involves using physiological signals, software algorithms and infusion devices (e.g. with a subcutaneous catheter, implanted device) and, in preferred embodiments, intranasal delivery, e.g. delivery to the mucosa of the nasal septum, particularly at Kiesselbach's plexus [also known as “Little's area”] and/or the nasal mucosa of the turbinates for the safe delivery of drugs which could potentially cause hypopnea, apnea and death if given in excess quantities. Since no single dose is appropriate for all individuals, and due to other medications and/or underlying clinical conditions, dosing without physiologic monitoring as disclosed herein, is unsafe. Furthermore, in the particular context of medical operations, the present invention provides a system, method and apparatus, herein referred to by the acronym TET (trauma environment treatment), in which operatives in trauma environment situations are able to receive appropriate pharmacologic intervention at a much earlier stage than has previously been possible. By coupling the PD, PK or PD+PK measurement sensors and signals of the present invention with the processor of this invention, and which then controls delivery of appropriate fluids and/or drugs to a subject, morbidity and mortality and potentially Post-traumatic Stress Disorder (PTSD) are substantially reduced.
In addition, by incorporating into TET a global positioning system, (GPS), a subject in need can be located, triaged, monitored, and optimally treated with drugs and/or fluids, either locally or remotely (e.g., rescue helicopters).
With respect to a further aspect of the present invention mentioned above, namely a system, method and apparatus combining PPG++SMART (photoplethysmography plus other physiologic parameters+Self Monitoring and Reporting Therapeutics), there is disclosed integration of SMART technology described with PPG-based acquisition of medically relevant subject parameters. The SMART technology is covered by at least the following patent documents, each of which is herein incorporated by reference, including, as appropriate, pending and issued international and national equivalents thereof:
U.S. Pat. No. 7,820,108, Marker Detection Method and Apparatus to Monitor Drug Compliance; US US20050233459, Marker Detection Method and Apparatus to Monitor Drug Compliance; US20070224128, Drug Adherence Monitoring System; WO2007103474, Medication Adherence Monitoring System; W02008103924, Medication Adherence Monitoring System; U.S. Pat. No. 7,104,963, Method and Apparatus for Monitoring Intravenous (IV) Drug Concentration Using Exhaled Breath.
The PPG+ technology described herein for integration with the SMART system, is covered by at least the following patent documents, each of which is herein incorporated by reference, including, as appropriate, pending and issued international and national equivalents thereof: U.S. Pat. No. 6,909,912, Non-Invasive Perfusion Monitor and System, Specially Configured Oximeter Probes, Methods of Using Same, and Covers for Probes; WO/2004/000114, Perfusion Monitor and System, Including Specifically Configured Oximeter Probes and Covers for Oximeter Probes; U.S. Pat. No. 7,127,278, and U.S. Pat. No. 7,024,235, Novel Specially Configured Lip/Cheek Pulse Oximeter/Photoplethysmography Probes, Selectively With Sampler for Capnography and Covering Sleeves for Same; US 2007-0027375 A1, Optimized Gas Supply Using Photoplethysmography; WO/2005/065540, Novel Specially Configured Nasal Pulse Oximeter; WO/2006/086010, METHODS AND DEVICES FOR COUNTERING GRAVITY INDUCED LOSS OF CONSCIOUSNESS AND NOVEL PULSE OXIMETER PROBES; (WO/2006/116469) METHOD AND APPARATUS FOR DIAGNOSING RESPIRATORY DISORDERS AND DETERMINING THE DEGREE OF EXACERBATIONS; US 2008-0067132 A1, Method for Using Photoplethysmography to Optimize Fluid Removal During Renal Replacement Therapy by Hemodialysis or Hemofiltration; (WO/2008/020845) METHODS AND DEVICES FOR CENTRAL PHOTOPLETHYSMOGRAPHIC MONITORING METHODS
With respect to infusion pumps, which are ubiquitous in hospitals and other healthcare settings, recently the FDA promulgated the “Infusion Pump Improvement Initiative” due to numerous reports of morbidity and mortality related to infusion pump (mis)use. See, for example,
http://www.fda.gov/MedicalDevices/ProductsandMedicalProcedures/GeneralHospitalDevicesandSupplies/InfusionPumps/default.htm
The predominant numbers of reported cases deal with PCA (Patient Controlled Analgesia) pumps, since such devices are designed to allow patients to self-administer, for example, opioids. While there are some control systems in place which limit the total dose of opioid and/or the frequency with which they are delivered, most dosing algorithms do not take into account all of the varying and relevant factors including, but not limited to, patient size and fitness (e.g., weight), pharmacokinetic interactions (Liberation, Adsorption, Distribution, Metabolism, and Elimination, LADME) that can alter opioid concentration in the blood, pharmacodynamic interactions (patient age, underlying medical conditions, including but not limited to undiagnosed obstructive or central sleep apnea, unusual sleep staging, cardiorespiratory disease, kidney or liver disease) that can markedly alter the biological sensitivity to opioids as well as active ingredients of medications in other medical classes.
Knowledge of these factors is required to properly calculate the appropriate (safe) dosing schedule of an opioid or such other medications for any particular patient. While this problem is particularly hazardous during opioid delivery, it can also occur in other medical settings where a patient is receiving intravenous (or medications administered by other routes such as epidural/intrathecal, and the like) medications and/or fluids, all of which have the potential of creating untoward and unexpected effects, especially when multiple medications are infused simultaneously or used in conjunction with many oral medications.
A 2005 review of PCA provides this summary of the potential dangers of this technology:
“Risk Factors for Respiratory Depression and Mishaps with IV-PCA
Several authors have summarized the risk factors for respiratory depression with IV-PCA. These risk factors can be categorized as “patient/disease related” and “technique/equipment” related. The patient/disease related risk factors apply regardless of route of opioid administration and include advanced age, head injury, sleep apnea syndrome, obesity, respiratory failure, concurrent use of sedative medications, especially benzodiazepines, hypovolemia, and renal failure. Unfortunately, avoidable instances of critical events continue to occur when IV-PCA alone is used. Some of the reasons include operator errors: programming errors (the most frequent mishap), accidental bolus administration during syringe change, inappropriate dose prescription or lockout interval, drug errors (wrong drug or wrong concentration), inappropriate drug selection (i.e., morphine or meperidine in a patient with renal failure), and disconnection or absence of Y-connector (allowing for accumulation of opioid in the IV tubing followed by intermittent bolus delivery). Common patient errors include activation of the PCA pump by others (i.e., family members), and failure to understand the device. Possible equipment problems include siphoning of drug (pump placed above patient without flow restriction valve or cracking of a glass syringe) and equipment failure resulting in spontaneous activation of drug delivery. A case report illustrates how IV-PCA can result in a lethal mishap. Vicente et al. describe a 19-yr-old woman who underwent uneventful cesarean section delivery, after which morphine IV-PCA was ordered. A drug cassette containing 1 mg/mL was unavailable, so the nurse substituted a cassette that contained 5 mg/mL. The patient was found dead 7.5 h later in her postpartum room. The available evidence was consistent with a programming error wherein morphine 1 mg/mL was entered instead of 5 mg/mL, thereby causing the pump to deliver a demand dose of 10 mg instead of 2 mg. Based on a search of the FDA Medical Device Reporting database and other sources and on a denominator of 22,000,000 PCA uses provided by the PCA device manufacturer, the authors estimated that mortality from user programming errors with this device is a small likelihood event (ranging from 1 in 33,000 to 1 in 338,800) but that it is relatively numerous in absolute terms (ranging from 65-667 deaths in the history of the use of the device). Clearly, mishaps with IV-PCA, mostly resulting from human error, remain a problem. To minimize the occurrence of these hazards, hospitals need to incorporate standard safety features into practice. Nursing staff on every ward must be trained in the safe use of PCA pumps and recognition and management of complications. Initial programming and setup of the pump and changes in programming require great care to prevent errors. It is common practice in most hospitals for a second nurse to witness and verify the initial programming and any changes in programming. Hospital pharmacies should formulate standard solutions of drug and send only those standard solutions to the wards. Patient and family education is important for safety, particularly instruction that only the patient should activate the PCA button”, see REVIEW ARTICLE Grass J A, Patient-Controlled Analgesia. ANESTH ANALG 2005; 101:S44-S61.
Presently, patients are almost always placed on supplemental oxygen due to concerns that they may hypoventilate due to respiratory depression induced by opioids. They are almost always placed on a pulse oximeter to measure oxygen saturation, and recently, some hospitals have used capnography with or without pulse oximetry. Unfortunately, oxygen desaturation, which may occur with opioid use (respiratory depression), is severely blunted by the use of supplemental oxygen, and it has been shown that end-tidal carbon dioxide measurements are unreliable in spontaneously breathing patients when a nasal canula or similar device is used for monitoring.
Accordingly, there is an instant and pressing unmet need by the medical community for a monitoring system which automatically integrates all the factors previously discussed that determine proper opioid dosing, which can reliably detect cardiorespiratory changes in real-time and provide a means to discontinue continuous (e.g., intravenous or epidural) infusions until a healthcare worker (HCW) can be alerted to impending cardiorespiratory failure and alleviate the situation. This system would significantly reduce or even eliminate both “patient/disease related” and “technique/equipment” related morbidity and mortality in the setting of infused therapy with opioids and other types of medications such as local anesthetics (e.g., epidural).
Attempts have been made in the art to address the needs outlined herein above with respect to this aspect of the invention. Thus, for example, U.S. Pat. No. 6,165,151 to Weiner, provides an Apparatus and Methods for Control of Intravenous Sedation. The Weiner system essentially provides a controller unit which receives a pulse oximetry signal from a subject and, based on that signal, controls a flow restrictor in contact with an IV line from a gravity fed medication source to a subject. As will be appreciated from a review of the complete disclosure which follows, the present system is designed to make a PCA pump safer by preventing a patient from overdosing with an opioid through their own volition, error or the like. Additionally, it provides a “safety net” should a healthcare worker accidently input the wrong infusion rate or give the wrong concentration of medication. The Weiner device is designed to go on a free flowing IV system which is inherently dangerous, and in any event, is a closed-loop system for medication delivery, which is distinguishable from at least one aspect of the present invention, which is a stand-alone safety device which can be used agnostically with any infusion pump or medication delivery system for delivery of medication to a subject from an external source. Furthermore, while the Weiner system uses a pulse oximeter for a feedback loop, this is also used in several PCA pumps such as the Alaris® system from CareFusion. The present system, as will be seen below, does not utilize pulse oximetry as the major means of monitoring, for example, opioid effects on a patient, since, as expanded upon below, pulse oximetry is notoriously a late signal to use for feedback (e.g. patients receiving oxygen can exhibit dangerously high CO2 levels resulting in respiratory depression or complete apnea without any change in oxygen saturation). Instead, in a preferred embodiment, the present invention, as disclosed below, utilizes a Single Point of Contact (SPOC) probe, preferably comprising a combination of Photoplethysmography (PPG) plus nasal airway pressure/flow and an accelerometer to detect early deleterious effects of, e.g. opioids (changes in I:E ratio [inspiratory to expiratory time], length of expiratory time, respiratory rate, etc.) none of which can be detected with a pulse oximeter.
In a variant to the Weiner U.S. Pat. No. 6,165,151 patent disclosure, Weiner also, in a subsequent patent publication, US2005/0027237, disclosed substantially the same system as disclosed in the '151 patent, but in use with a blood pressure monitoring system to assist in treating patients suffering potentially catastrophic blood and/or fluid loss. The same or similar considerations as noted above apply to this publication as well. Blood pressure monitoring is of little value in determining when to discontinue an opioid infusion, as changes in blood pressure are a late sign and respiratory not cardiovascular effects predominate. In the setting of catastrophic blood loss, an ideal closed-loop system would maximize fluid delivery, but depending on the medication being infused this could, in itself, lead to catastrophic outcomes if, for instance, a medication to lower blood pressure was being infused. Finally, in most circumstances blood pressure is a late finding during blood loss, while the instant invention uses sensing technology that detects impending hypovolemic shock rather than shock after it has occurred.
In WO2007/033025, and in related US2009/0177146 to Nesbitt et al., a system substantially similar to the Weiner system was disclosed as a closed-loop system for controlling a pump-delivered medication to a subject whose vital signs from physiological monitors attached to a patient. That system includes an occlusion sensor, and in relation to the Weiner system, confirms our observations above, that the device of Weiner “fails to monitor many patient vital signs such as blood pressure, temperature, respiration rate, and capnography readings . . . . A lone pulse oximetry device may not be able to accurately assess the true condition of the patient, leaving the patient vulnerable to improper controller adjustments of fluid flow rate.” To cure these acknowledged defects in the Weiner system, Nesbitt et al., propose a system in which, in addition to or in place of a pulse oximeter, there is included a breath analyzer, for analyzing, for example, propofol in the breath of a subject, according to US20050022811 (Kiesele et al), for analyzing CO2, O2 volume flow, temperature sensor, an ECG electrode and a photo-plethysmography (PPG) device to generate Pulse Transit Time (PTT), and the like. This system too, while on first inspection appears similar to an aspect of the system we describe herein, is likewise distinguishable as it requires careful integration of the physiological sensors connected to the patient with the fluid delivery system—in a closed-loop or advisor controlled medication delivery system. Accordingly, the Nesbitt et al., solution is not an agnostic solution which can be utilized as a “bolt-on” safety device for use with any existing fluid infusion system.
Finally, it is worth noting that Hickle et al., US2003/0040700, likewise discloses a highly complex, closed-loop infusion system for a patient which is likewise dependent on careful integration of patient physiologic monitors with the infusion system, and thus suffers from the same issues noted above in connection with the Nesbitt et al., system. By contrast, the present system is simple and focuses on one problem—shutting off flow from the medication source if there is a trend towards cardiorespiratory depression, without having to integrate a number of vital sign parameters into an infusion device, which would be highly complex and require a great deal of skill to be exercised by the user even if algorithms are written to control the pump.
Accordingly, in the present patent disclosure, we provide a system for use of photoplethysmography (PPG) and/or other cardiorespiratory signals (nasal airway pressure [NAP] or flow [NAF]) and the addition of an accelerometer, preferably at a single point of contact (SPOC), preferably the nasal alae, to monitor cardiorespiratory function during infusion therapy. Furthermore, we provide an improvement to such a system wherein the improvement includes, in addition to the monitoring system, a small device (pneumatic, mechanical or otherwise actuated) that is connected to intravenous (or epidural/intrathecal) tubing running between an infusion pump and a patient to “pinch” the tubing, thus disrupting the flow of the opioid (or other medication or fluids) until a HCW intervenes, without requiring any other (e.g. electronic) integration with the fluid/medication delivery system. With this approach, we propose an “infusion pump agnostic” solution to this pressing medical need which does not require imposing design and regulatory burdens on infusion pump manufacturers. We further believe that the FDA will embrace a straightforward solution that can be implemented on all infusion pumps in a timely manner.
In addition to the various aspects of this invention discussed above, and how these aspects differ from reports in the patent or technical literature, this patent disclosure provides a medication agnostic safety system which, in various embodiments, can control the level of medication infusion into a subject, based on real-time or as near to real-time as possible measurement of subject physiological condition, and which, in the same or different embodiments, can initiate supplemental safety measures, including, for example, reduction in or cessation of medication delivery, and, as appropriate, initiation of positive airway pressure or similar forms of ventilation, when such is called for. Accordingly, this invention provides a solution to the long-felt need for a safe system, either in an advisory capacity for trained staff or in a control capacity, to improve the safety of medication administration.